Pulmonary diseases represent a large portion of neonatal and adult morbidity and mortality. Many of these have no cure, and new therapeutic approaches are desperately needed. De-cellularization of whole organs, which removes cellular elements but leaves intact important extracellular matrix (ECM) proteins and three-dimensional architecture, has recently been investigated for ex vivo generation of lung tissues. As specific cell culture surfaces, including ECM composition, profoundly affect cell differentiation, this approach offers a potential means of using de-cellularized lungs to direct differentiation of embryonic and other types of stem/progenitor cells into lung phenotypes. Several different methods of whole-lung de-cellularization have been reported, but the optimal method that will best support re-cellularization and generation of lung tissues from embryonic stem cells (ESCs) has not been determined. We present a 24-h approach for de-cellularizing mouse lungs utilizing a detergentbased (Triton-X100 and sodium deoxycholate) approach with maintenance of three-dimensional lung architecture and ECM protein composition. Predifferentiated murine ESCs (mESCs), with phenotypic characteristics of type II alveolar epithelial cells, were seeded into the de-cellularized lung scaffolds. Additionally, we evaluated the effect of coating the de-cellularized scaffold with either collagen or Matrigel to determine if this would enhance cell adhesion and affect mechanics of the scaffold. Finally, we subcutaneously implanted scaffolds in vivo after seeding them with mESCs that are predifferentiated to express pro-surfactant protein C (pro-SPC). The in vivo environment supported maintenance of the pro-SPC-expressing phenotype and further resulted in vascularization of the implant. We conclude that a rapid detergent-based de-cellularization approach results in a scaffold that can maintain phenotypic evidence of alveolar epithelial differentiation of ESCs and support neovascularization after in vivo implantation.
For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the goal of regenerating functional tissues. Several decellularization strategies have been employed for lung, however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells, and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed.
Introduction: Nuss procedure, a minimally invasive thoracoscopic approach to repair pectus excavatum, results in a smaller scar but significant pain. The purpose of this Institutional Review Boardapproved retrospective study was to compare postoperative pain management outcomes of adolescents who self-selected to receive or not receive preoperative self-hypnosis training before Nuss procedure. Self-hypnosis, an integrative medicine approach to pain management, may be more effective than traditional analgesics alone for managing postoperative pain. Methods:In 2011, 8 of 22 patients who underwent Nuss procedure received preoperative self-hypnosis training and postoperative self-hypnosis coaching. Postoperatively, patients received epidural analgesia with local anesthetic, intravenous patient-controlled opioid analgesia, and intravenous nonsteroidal anti-inflammatory drugs and transitioned to oral opioids and nonsteroidal anti-inflammatory drugs.Results: Self-hypnosis training was associated with use of fewer milligrams per hour of morphine equivalents ( p = .005) and lower mean pain intensity over the first 5 days of hospital stay ( p = .041). Despite the opioid-sparing effect of self-hypnosis training, nausea, vomiting, constipation, and hypoventilation were adverse effects experienced by patients in both groups. Discussion:The results of this retrospective study suggest that selfhypnosis provides an opioid-sparing effect for managing moderateto-severe pediatric postoperative pain after Nuss procedure. Further clinical studies are needed to validate the effectiveness of self-hypnosis for symptom management after painful pediatric surgical procedures.
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